TOPLINE

Haptoglobin and immunoglobulin A2 (IgA2) independently predicted a composite outcome of major adverse cardiovascular events (MACE) and all-cause death in asymptomatic adults. Those with high levels of both proteins experienced approximately twice the rate of events compared with those with low levels. These associations remained significant even after accounting for traditional risk factors and vascular imaging results.

METHODOLOGY

• Researchers aimed to validate the association of haptoglobin and IgA2 with subclinical atherosclerosis in a US cohort and to test whether these plasma proteins can independently predict cardiovascular outcomes beyond the Framingham risk score or vascular imaging findings.
• The analysis included 5328 US adults (mean age, 69 years; 56.9% women) without cardiovascular symptoms from the BioImage study.
• At baseline, participants underwent ultrasound imaging to assess carotid plaque burden, CT to quantify coronary artery calcium, and immunoassay testing to measure haptoglobin and IgA2 levels in plasma.
• The primary outcome was a composite of MACE and all-cause death, assessed over a median follow-up duration of 4.6 years.

TAKEAWAY

• Higher levels of haptoglobin and IgA2 were associated with greater burden of carotid plaque and coronary artery calcium, even after adjusting for the Framingham risk score.
• During follow-up, 8.8% of participants had the composite outcome of MACE and all-cause death.
• Both haptoglobin and IgA2 remained significant independent predictors of the composite outcome even after adjustment for carotid plaque burden or coronary artery calcium (P < .05 for both).
• Discrimination for the composite outcome, measured by Harrell C statistic, improved modestly beyond the Framingham risk score alone — from 0.621 to 0.629 with the addition of haptoglobin and to 0.623 with the addition of IgA2; the combination of haptoglobin, IgA2, and high-sensitivity C-reactive protein produced the largest gain, raising the C statistic to 0.638.
• Adults with levels of haptoglobin ≥ 1.3 g/L and IgA2 ≥ 380 mg/L had roughly twice the rate of events compared with those with both proteins below median levels.

IN PRACTICE

"Our findings suggest that haptoglobin and IgA2, along with hs-CRP [high-sensitivity C-reactive protein], could serve as accessible biomarkers of residual immune-inflammatory risk, potentially guiding personalized preventive therapies," the researchers wrote.

SOURCE

The study was led by Ana García-Álvarez, MD, PhD, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain. It was published online on September 9 in the Journal of the American Heart Association.

LIMITATIONS

Researchers relied on insurance claims data for adverse events and may have missed some events. The study followed participants for a relatively shorter duration. The BioImage study cohort included mainly White and older adults, which may have limited the applicability of the findings to broader populations.

DISCLOSURES

The study was supported by grants from Spain's Ministerio de Ciencia, Innovación y Universidades, the Instituto de Salud Carlos III, and other sources. One author declared being an employee of Philips, and another declared being the CEO of SQ Innovation; neither company had a role in the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.